Piperazines of formula A
wherein R is a lower alkyl, Ar is an unsubstituted or substituted aryl or heteroaryl, and Q is a hydrogen, CO-(lower) alkyl, CO-cycloaklyl, or CO-aryl, and * indicates a chiral center are potent 5HT1A receptor binding agents. U.S. Pat. No. 6,127,357 teaches piperazine derivatives that are useful in the treatment of Central Nervous System (CNS) disorders. Enantiomers of such piperazines can display different binding abilities to 5HT1A receptors. Therefore, their potency, selectivity, and metabolic effects may be different. WO 9703982 teaches that certain enantiomers of such piperazines display improved 5HT1A binding affinity and bioavailability. Therefore, an efficient, operationally facile, inexpensive and safe alternative process for making the optically preferred piperazines is desirable.
WO 9533725 teaches a method for synthesizing some chiral piperazines of formula A by alkylation of the corresponding 1-aryl-piperazine with enantiomerically pure 2-(5-methyl-2,2-dioxido-1,2,3-oxathiazolidin-3-yl)pyridine. WO 9533725 also teaches nucleophilic ring openings of sulfamidates with 1-aryl-piperazine and opening with various primary and secondary amines is known form L. T. Boulton, J. Chem. Soc., Perkin Trans. 1, 1999, 1421-1429.
WO 97/37655 and Cignarella et al., Farmaco Ed. Sci.; 31; 1976; 194, 196 discuss preparation and reaction of N1-(2′pyridyl)-1,2-propane-diamine.